本文選題：腎間質(zhì)纖維化 + 單側(cè)輸尿管梗阻��； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：目的：探討caspase-1和PARP1在腎間質(zhì)纖維化中的作用及其機(jī)制。 方法：將C57BL/6J野生型小鼠和caspase-1-/-型小鼠分別制備單側(cè)輸尿管梗阻(uuo)模型,共分為4組：野生型假手術(shù)組(WT sham-operated);野生型模型組(WT UUO); caspase-1-/-型假手術(shù)組(KO sham-operated)和caspase-1-/-型模型組(KO UUO).7天后處死小鼠取腎組織標(biāo)本,應(yīng)用Western Blot檢測(cè)caspase-7表達(dá)及激活水平、PARP1剪切與激活水平和α-SMA表達(dá)；免疫組化檢測(cè)α-SMA和fibronectin的表達(dá)和分布；Masson染色檢測(cè)膠原纖維的表達(dá)與分布；熒光實(shí)時(shí)定量PCR檢測(cè)α-SMA mRNA表達(dá)水平。 結(jié)果：(1)與WT sham-operated組相比,WT UUO組激活型caspase-7表達(dá)明顯上調(diào),差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。KO UUO組與WT UUO組相比,caspase-7激活明顯減少(P0.05),且α-SMA蛋白表達(dá)水平和mRNA表達(dá)下調(diào)(P0.05),而PARP1的剪切和激活并無(wú)明顯變化。(2)免疫組化結(jié)果顯示：與WT sham-operated組比,WT-UUO組α-SMA和fibronectin表達(dá)增加,而KOUUO組與WTUUO組相比,α-SMA和fibronectin表達(dá)明顯減少(P0.05)。 Masson染色結(jié)果表明,KOUUO組與WTUUO組相比,膠原含量減少(P0.05)。 結(jié)論：Caspase-1基因敲除可降低caspase-7的活性,并使α-SMA和fibronectin表達(dá)下調(diào),但對(duì)PARP1的激活無(wú)明顯影響。這提示caspase-1-caspase-7信號(hào)通路在腎纖維化中起重要作用。
[Abstract]:Objective: to investigate the role and mechanism of caspase-1 and PARP1 in renal interstitial fibrosis. Methods: C57BL/6J wild-type mice and caspase-1-r-type mice were used to establish unilateral ureteral obstruction models. The mice were divided into four groups: wild type sham-operated group (WT sham-operated) group; wild type model group (WWT UUO); caspase-1-r-type sham-operated group (KO sham-operated group) and caspase-1-r-type model group (Caspase-1-r-type model group). The expression and distribution of 偽 -SMA and 偽 -SMA were detected by Western Blot, the expression and distribution of 偽 -SMA and 偽 -SMA by immunohistochemistry, and the expression of 偽 -SMA mRNA by real-time fluorescence quantitative PCR. Results compared with WT sham-operated group, the expression of activated caspase-7 increased significantly in WT UUO group. Compared with WT UUO group, the activation of caspase-7 in KO UUO group was significantly lower than that in WT UUO group, and the expression level of 偽 -SMA protein and mRNA expression were down-regulated in P0.05, while the shear and activation of PARP1 had no significant change. The immunohistochemical results showed that: compared with WT sham-operated group, the expression of 偽 -SMA protein was lower than that of WT sham-operated group. The expression of 偽 -SMA and fibronectin increased in WT-UO group. The expression of 偽 -SMA and fibronectin in KOUUO group was significantly lower than that in WTUUO group. The results of Masson staining showed that the content of collagen in KUO group was lower than that in WTUUO group. Conclusion the knockout of the Caspase-1 gene can decrease the activity of caspase-7 and down-regulate the expression of 偽 -SMA and fibronectin, but has no effect on the activation of PARP1. This suggests that caspase-1-caspase-7 signaling pathway plays an important role in renal fibrosis.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R692.6

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